Hepcludex - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Hepcludex 2 mg powder for solution for injection bulevirtide

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Hepcludex is and what it is used for

• 2. What you need to know before you take Hepcludex

• 3. How to take Hepcludex

• 4. Possible side effects

• 5. How to store Hepcludex

• 6. Contents of the pack and other information

• 7. Step-by-step injection guide

1. What Hepcludex is and what it is used for

What Hepcludex is

Hepcludex contains the active substance bulevirtide, which is an antiviral medicine.

What Hepcludex is used for

Hepcludex is used to treat long-term (chronic) hepatitis delta virus (HDV) infection in adults with compensated liver disease (when the liver is still working well enough). Infection with hepatitis delta virus causes inflammation of the liver.

How Hepcludex works

HDV uses a particular protein in liver cells to enter the cells. Bulevirtide, the active substance in this medicine blocks the protein and so prevents the HDV from getting into liver cells. This reduces the spread of HDV in the liver and reduces inflammation.

2. What you need to know before you take Hepcludex

Do not take Hepcludex:

• – if you are allergic to bulevirtide or any of the other ingredients of this medicine (listed in section

6).

If you are not sure, speak to your doctor before taking this medicine.

Warnings and precautions

Do not stop your treatment with Hepcludex unless your doctor advises you to do so. Stopping the treatment can reactivate the infection and worsen your disease.

Talk to your doctor or pharmacist before taking Hepcludex:

• if your liver is not working well enough – it is not known how well Hepcludex works in these circumstances; if your liver is not functioning well, taking Hepcludex is not recommended.
• if you have had kidney disease or if tests have shown problems with your kidneys. Before and during treatment, your doctor may order blood tests to check how well your kidneys are working;
• if you have HIV infection or hepatitis C – it is not known how well Hepcludex works in these circumstances; your doctor may order blood tests to check the status of your HIV or hepatitis C infection
• if you get reactions such as swelling, redness, irritation, bruising, itchiness, infection or pain at the injection site – this medicine is given by injection under the skin.
• if you have an elevation of bile acids in the blood. Hepcludex increases the level of bile acids in the blood – the long-term effect of bile acid elevation is not known.

Children and adolescents

Children and adolescents under 18 years of age should not be treated with Hepcludex.

Other medicines and Hepcludex

Please tell your doctor if you are taking, have recently taken, or might take any other medicines.

Some medicines can increase side effects of Hepcludex and you should not take them at the same time. This is why you should tell your doctor if you are taking any of these medicines:

• ciclosporin, a medicine that supresses the immune system;
• ezetimibe, used for treating high blood cholesterol;
• irbesartan, used for treating high blood pressure and heart disease;
• ritonavir, used to treat HIV infection;
• sulfasalazine, (used for treating rheumatoid arthritis, ulcerative colitis, and Crohn's disease.

Some medicines can increase or decrease the effects of Hepcludex when taken together. In some cases, you may need to have certain tests or your doctor may change the dose or monitor you regularly:

• cancer treatments (e.g. dasatinib, docetaxel, ibrutinib, paclitaxel);
• antihistamine medicines used for allergies (e.g. ebastine, fexofenadine);
• immune system medicines (e.g. everolimus, sirolimus, tacrolimus);
• medicines for hepatitis C and HIV treatment (e.g. darunavir, glecaprevir, grazoprevir, indinavir, maraviroc, paritaprevir, saquinavir, simeprevir, tipranavir, voxilaprevir);
• medicines for diabetes (e.g. glibenclamide, nateglinide, repaglinide);
• medicines for erectile dysfunction (e.g., avanafil, sildenafil, vardenafil);
• medicines for treating high blood pressure and heart disease (e.g. olmesartan, telmisartan, valsartan);
• statin, medicines used for high blood cholesterol (e.g. atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin);
• thyroid hormones used to treat thyroid problems;
• alfentanil, an opioid medicine used to treat severe pain;
• bosentan, used for pulmonary arterial hypertension;
• buspirone, an anxiety medicine;
• budesonide, used for asthma and chronic obstructive pulmonary disease;
• conivaptan and tolvaptan, used to treat hyponatraemia (low sodium levels);
• darifenacin, used to treat urinary incontinence;
• dronedarone, heart medicine for cardiac arrhythmias;
• eletriptan, used for migraine headaches;
• eplerenone, used for high blood pressure;
• estrone-3-sulfate a menopausal hormone medicine;
• felodipine and nisoldipine (heart medicines);
• lomitapide, used for high blood cholesterol;
• lurasidone and quetiapine, antipsychotic medicines for psychiatric disorders;
• midazolam and triazolam, medicines to treat insomnia (inability to sleep) and for anaesthesia (to avoid pain during surgery);
• naloxegol, used to treat dependence on opioid medicines for severe pain;
• ticagrelor, anticoagulant to prevent blood clotting.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You should not use this medicine unless specifically told to by your doctor.

If you are a woman of childbearing potential, you should not take this medicine without using an effective method of contraception.

Talk to your doctor to decide whether you should breastfeed while taking Hepcludex.

It is not known whether Hepcludex can pass into breast milk. Therefore, a decision must be made whether to discontinue breastfeeding or to discontinue Hepcludex.

Driving and using machines

Dizziness and tiredness are side effects which may impair your ability to drive and use machines. If you have any concerns consult your doctor.

Sodium content

This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially „sodium-free“.

3. How to take Hepcludex

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

Dosage

The recommended dose is 2 mg once daily by subcutaneous injection (just under the skin). Your doctor will say how long you need to take the medicine for.

Your doctor and nurse will show you how to prepare and inject Hepcludex. This package leaflet contains a step-by-step injection guide to help you inject the medicine (see Section 7).

If you take more Hepcludex than you should

The usual dose is 2 mg (1 vial) per day. If you think you may have taken more than you should, tell your doctor immediately.

If you forget to take Hepcludex

If less than 4 hours have passed since your missed dose of Hepcludex, take the missing dose as soon as possible and take your next scheduled dose at the usual time.

If more than 4 hours have passed since your missed dose of Hepcludex, do not take the missed dose. Take the next dose the following day at the usual time. Do not take a double dose to make up for the missed dose. Tell your doctor if you have missed a dose of Hepcludex.

Do not stop taking Hepcludex without speaking with your doctor

If you do not want to take Hepcludex anymore, talk to your doctor before stopping the treatment. Stopping the treatment can reactivate the infection and worsen your disease. Tell your doctor immediately about any changes in symptoms after stopping treatment.

If you have any further questions on the use of Hepcludex, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Please tell your doctor if any of the side effects occur, or if you notice any side effects not listed in this leaflet.

The following side effect is very common (this may affect more than 1 in 10 people):

• an increase in the level of bile acids in the blood.

The following side effects are common (these may affect up to 1 in 10 people):

• headache
• dizziness
• nausea
• tiredness
• sleepiness
• faster than normal heartbeat (tachycardia)
• flu-like illness
• swollen abdomen (belly)
• itching
• joint pain
• muscle spasms
• reactions at the injection site that may include swelling, redness, irritation, bruising, itchiness, infection or pain
• excessive or uncontrolled sweating
• blood in urine
• redness of the skin
• rash.

Blood tests may also show:

• an increase in liver enzyme levels and bilirubin in the blood. These are usually raised in most diseases that cause damage to the liver;
• a decrease in red blood cells (anaemia);
• a reduction in immature red blood cells (reticulocytes);
• a reduction in white blood cells (eosinophils, lymphocytes, neutrophils), or platelets (thrombocytes) in the blood;
• a reduction in the level of haemoglobin in the blood ;
• an increase in the level of amylase and lipase in the blood (signs of possible pancreas damage);
• an increase of the international normalised ratio (INR) for blood clotting (which increases the risk of bleeding and bruising);
• An increase in the level of creatinine in the blood (a sign of kidney damage).

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help to provide more information on the safety of this medicine.

5. How to store Hepcludex

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C –8°C). In order to protect from light, keep the vials in the outer carton.

The reconstituted solution should be used immediately. However, if this is not possible it can be stored for up to 2 hours at a temperature of up to 25°C.

Do not throw away any medicines or used needles via wastewater or household waste. Ask your pharmacist how to safely dispose medicines and used needles.

6. Contents of the pack and other information

What Hepcludex contains

The active substance is bulevirtide 2 mg. Each vial contains bulevirtide acetate equivalent to 2 mg bulevirtide.

The other ingredients are: sodium carbonate anhydrous, sodium hydrogen carbonate, mannitol, hydrochloric acid, sodium hydroxide.

What Hepcludex looks like and contents of the pack

Bulevirtide is a powder for solution for injection and comes as a white to off-white powder.

Each carton contains 30 single doses.

Marketing Authorisation Holder

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Manufacturer

LYOCONTRACT GmbH

Pulverwiese 1

38871 Ilsenburg

Germany

or

Gilead Sciences Ireland UC

IDA Business and Technology Park

Carrigtohill

Co. Cork

Ireland

For any information about this medicine, please

Authorisation Holder:

Belgie/Belgiqu­e/Belgien

Gilead Sciences Belgium SRL-BV

Tél/Tel: + 32 (0) 24 01 35 50

Etnrapua

Gilead Sciences Ireland UC

Ten.: + 353 (0) 1 686 1888

Česká republika

Gilead Sciences s.r.o.

Tel: + 420 (0) 910 871 986

Danmark

Gilead Sciences Sweden AB

Tlf: + 46 (0) 8 5057 1849

Deutschland

Gilead Sciences GmbH

Tel: + 49 (0) 89 899890–0

Eesti

Gilead Sciences Poland Sp. z o.o.

Tel.: +48 (0) 22 262 8702

EZZáSa

Gilead Sciences EZZág M.EnE.

Tql: + 30 (0) 210 8930 100

España

Gilead Sciences, S.L.

Tel: + 34 (0) 91 378 98 30

France

Gilead Sciences

Tél: + 33 (0) 1 46 09 41 00

Hrvatska

Gilead Sciences Ireland UC

Tel: + 353 (0) 1 686 1888

contact the local representative of the Marketing

Lietuva

Gilead Sciences Poland Sp. z o.o.

Tel.: + 48 (0) 22 262 8702

Luxembourg/Lu­xemburg

Gilead Sciences Belgium SRL-BV

Tel/Tel: + 32 (0) 24 01 35 50

Magyarorszag

Gilead Sciences Ireland UC

Tel.: + 353 (0) 1 686 1888

Malta

Gilead Sciences Ireland UC

Tel: + 353 (0) 1 686 1888

Nederland

Gilead Sciences Netherlands B.V.

Tel: + 31 (0) 20 718 36 98

Norge

Gilead Sciences Sweden AB

Tlf: + 46 (0) 8 5057 1849

Österreich

Gilead Sciences GesmbH

Tel: + 43 (0) 1 260 830

Polska

Gilead Sciences Poland Sp. z o.o.

Tel.: + 48 (0) 22 262 8702

Portugal

Gilead Sciences, Lda.

Tel: + 351 (0) 21 7928790

Romania

Gilead Sciences Ireland UC

Tel: + 353 (0) 1 686 1888

Ireland

Gilead Sciences Ireland UC

Tel: + 353 (0) 214 825 999

island

Gilead Sciences Sweden AB

Simi: + 46 (0) 8 5057 1849

Italia

Gilead Sciences S.r.l.

Tel: + 39 02 439201

Kvnpog

Gilead Sciences EXXag M.EnE.

Tql: + 30 (0) 210 8930 100

Latvija

Gilead Sciences Poland Sp. z o.o.

Tel.: + 48 (0) 22 262 8702

Slovenija

Gilead Sciences Ireland UC

Tel: + 353 (0) 1 686 1888

Slovenská republika

Gilead Sciences Slovakia s.r.o.

Tel: + 421 (0) 232 121 210

Suomi/Finland

Gilead Sciences Sweden AB

Puh/Tel: + 46 (0) 8 5057 1849

Sverige

Gilead Sciences Sweden AB

Tel: + 46 (0) 8 5057 1849

United Kingdom (Northern Ireland)

Gilead Sciences Ireland UC

Tel: + 44 (0) 8000 113 700

This leaflet was last revised in < {MM/YYYY }><{month YYYY }>.

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

<Other sources of information>

Detailed information on this medicine is available on the European Medicines Agency web site: <, and on the website of {name of Member State Agency (link)}>. <There are also links to other websites about rare diseases and treatments.>

<→ <The following information is intended for healthcare professionals on­ly:>

• 7. Step-by-step injection guide